Administration Of Mitomycin Research Articles

Quantitative analysis of γH2AX reveals distinct responses in multiple mouse organs after administration of mitomycin C or ethyl methanesulfonate.

Ser139-phosphorylated H2AX (γH2AX) is a functional biomarker of DNA double-strand breaks. However, its conventional detection for in vivo samples relies on immunological methods using anti-γH2AX antibodies, making quantitative analysis difficult. Here, we established an absolute γH2AX quantification in vivo method for multiple organs in mice using liquid chromatography-triple quadrupole tandem mass spectrometry. When applying the method to male Institute of Cancer Research (ICR) mice (8 weeks old), the testes showed the highest γH2AX level (2.3% of total H2AX), followed by the bone marrow (0.51%), stomach (0.28%), kidney (0.20%), spleen (0.20%), liver (0.15%) and lung, which had the lowest overall level (0.10%). After intraperitoneal administration of 2 mg/kg mitomycin C in mice, γH2AX levels increased until 2-4 h, followed by a monotonical decrease to the control level in the bone marrow and spleen, and increased moderately until 24 h, followed by a slight decrease by 48 h in the liver, stomach, lung and kidney. After oral administration of 400 mg/kg ethyl methanesulphonate, γH2AX levels increased until 8 h and then decreased to the control level by 24-48 h in the spleen and kidney, increased until 24 h and then slightly decreased until 48 h in the bone marrow and lung, increased until 8 h and plateaued by 48 h in the liver, and decreased until 8 h and then increased to the control level in the stomach. Both the genotoxic chemicals did not alter γH2AX levels in the testes. These results indicate that our novel method could reveal variation in the γH2AX state in mouse organs and allows monitoring of the in vivo dynamics induced by genotoxic chemicals.

Ex vivo assays to predict enhanced chemosensitization by hyperthermia in urothelial cancer of the bladder.

IntroductionBladder cancer (urothelial carcinoma) is a common malignancy characterized by high recurrence rates and intense clinical follow-up, indicating the necessity for more effective therapies. Current treatment regimens include intra-vesical administration of mitomycin C (MMC) for non-muscle invasive disease and systemic cisplatin for muscle-invasive or metastatic disease. Hyperthermia, heating a tumor to 40–44°C, enhances the efficacy of these chemotherapeutics by various modes of action, one of which is inhibition of DNA repair via homologous recombination. Here, we explore whether ex vivo assays on freshly obtained bladder tumors can be applied to predict the response towards hyperthermia.Material and methodsThe cytochrome C release assay (apoptosis) and the RAD51 focus formation assay (DNA repair) were first established in the bladder cancer cell lines RT112 and T24 as measurements for hyperthermia efficiency, and subsequently tested in freshly obtained bladder tumors (n = 59).ResultsHyperthermia significantly increased the fraction of apoptotic cells after cisplatin or MMC treatment in both RT112 and T24 cells and in most of the bladder tumors (8/10). The RAD51 focus formation assay detected both morphological and numerical changes of RAD51 foci upon hyperthermia in the RT112 and T24 cell lines. In 64% of 37 analyzed primary bladder tumor samples, hyperthermia induced similar morphological changes in RAD51 foci.ConclusionThe cytochrome C assay and the RAD51 focus formation assay are both feasible on freshly obtained bladder tumors, and could serve to predict the efficacy of hyperthermia together with cytotoxic agents, such as MMC or cisplatin.

Conjunctvial lesions - The Relationship of Papillomas and Sguamous Cell Carcinoma to the HPV Infection

The etiology of papilloma formation is multifactorial. There is a strong association between human papillomavirus (HPV) and the development of these conjunctival lesions. HPV is tumorigenic and commonly produces benign tumors with low malignant potential. Papillomas rarely go through malignant transformation.Retrospective study of patients with a diagnosis of conjunctival papilloma or squamous cell carcinoma.From a collection of 125 patients with conjunctival non-pigmented tumours in the period from 2007 to 2017, in 119 (95.2%) patients histological examination confirmed papilloma and in 6 (4.8%) patients it confirmed carcinoma. Of the total number of patients, 39 were women (31.2%) and 86 men (68.8%). The mean age of patients was 68.4 years (range 20-94 years). Localization of lesions: bulbar conjunctiva - 65 (52.0%), upper eyelid tarsal conjunctiva + fornix - 6 (4.8%), lower eyelid + fornix - 27 (21.6%), caruncle - 20 (16.0%) and plica semilunaris - 7 (5.6%) patients. In the patient cohort we recorded 2 papillomas that were transformed into squamous cell carcinoma. HPV16 was positive in these patients, the carcinomas were from the area of the bulbar conjunctiva, and the surgical solution was associated with the perioperative administration of Mitomycin C. In one case, the inverted papilloma developed into orbital carcinoma within 2 years of primary excision, and the patient underwent radical surgical procedure (partial exenteration of the orbit) followed by radiotherapy.Transformation of the papilloma into the carcinoma is rare, but it must always be taken into consideration in case of a recurrence of the disease. HPV can infect the conjunctiva. The ophthalmologist, in collaboration with a pathologist, may recommend appropriate laboratory tests to confirm the diagnosis. Long-term outpatient follow-up of patients after excision of the conjunctival papilloma is also necessary. Key words: epibulbar tumors, conjunctival tumors, papilloma, carcinoma.

Single ablative intravesical electromotive mitomycin C administration for small non-muscle-invasive bladder cancer: a prospective study

Objectives To explore the effect of electromotive drug administration of mitomycin C (EMDA-MMC) using a single dose of intravesical mitomycin C (MMC) to avoid transurethral resection (TURBT) for small non-muscle-invasive bladder cancer.Material and methods All patients presenting small (<2 cm), single or multiple papillary bladder tumors were proposed to undergo a single EMDA-MMC instillation with 60 mg MMC before planning TURBT. The end point is complete disappearance of all papillary tumors at 2–4 weeks after EMDA-MMC.Results Thirty-six instillations were given to 32 patients. In general the treatment was well supported, except for two patients who had severe bladder spasms, resulting in early evacuation of the MMC. Complete response occurred in 28% (10/36 instillations). In 4 EMDA-MMCs with multiple tumors some tumors disappeared while others remained. In 61% (22/36) the tumors remained unchanged.Conclusion A single EMDA-MMC in l papillary bladder tumors <2 cm gives insufficient ablative effect.

Endocavitary prophylaxis of superficial urothelial bladder tumours: new compounds

Bladder urothelial carcinoma is the fourth most frequent cancer among European men, accounting for about 7% of the total cancers. Transurethral resection (TUR) is usually indicated as the standard treatment for non-muscle invasive bladder cancer (NMIBC). However, TUR is unable to guarantee a complete eradication of Ta, T1 tumors with a recurrence rate ranging from 50 to 70%, and a progression rate to muscle invasive disease ranging from 10 to 15%. METHODS. The European Association of Urology guidelines recommend adjuvant intravesical chemotherapy after definitive diagnosis of intermediate/high risk NMIBC to reduce both recurrence and progression of the disease. To provide a comprehensive review of intravesical treatment options for NMIBC, we performed a search of the PubMed database for articles between 1980 and 2009 that reported on intravesical agents for treating this disease. RESULTS. A critical analysis of the findings resulting from large multicenter trials, phase I, II, III studies for pertinent novel agents and from review articles was carried out. We focused on the following issues: 1) the role of the treatment with Bacillus Calmette-Guérin (BCG) and the need of maintaining the drug schedule (with or without interferon- alpha); 2) the correct timing of adjuvant immuno- and chemotherapy; 3) the use of the novel chemotherapeutic agents; 4) the use of the novel technique of chemotherapeutic agents administration, with a particular interest on electromotive administration of mitomycin.

Impact of age on outcomes of patients with non–muscle-invasive bladder cancer treated with immediate postoperative instillation of mitomycin C

ObjectivesTo evaluate whether age affects the clinical benefit afforded by immediate postoperative intravesical instillation of mitomycin C in a contemporary cohort of patients with NMIBC. Patients and methodsA total of 4,258 patients with NMIBC treated with transurethral resection of the bladder with (n = 2,605, 61%) or without (n = 1,652, 39%) one immediate instillation of mitomycin C from 5 institutions (study period: 2000–2007) were included. No patients received adjuvant instillations. A multivariable Cox proportional hazards regression model adjusting for standard clinical and pathological features tested the potential interaction term between age and administration of mitomycin C with regard to disease recurrence. ResultsA total of 2,063 patients experienced disease recurrence with a median follow-up of 48 months for those who did not recur. In multivariable Cox regression analysis, immediate postoperative instillation of mitomycin C (HR: 0.62; 95% CI: 0.56–0.68; P<0.0001) and age (HR: 1.04; 95% CI: 1.00–1.09; P = 0.036) were associated with disease recurrence. We observed only slight decreases in recurrence-free survival with age irrespective of treatment administration of mitomycin C or not. ConclusionWe confirmed reduced disease recurrence rates associated with 1 immediate postoperative intravesical instillation of mitomycin C in NMIBC patients. The benefit on recurrence-free survival of a postoperative intravesical instillation was preserved across all ages and therefore age by itself should not be taken into consideration when deciding to use it.

Letter to the Editor: Corneoscleral Melt 50 Years after Excision of Pterygium.

Purpose:To report a case of corneoscleral melt that occurred 50 years after resection of pterygium with postoperative administration of mitomycin C (MMC).Results:A 93-year-old woman developed acute corneal perforation and scleral melt in her left eye at 50 years after pterygium surgery with postoperative topical MMC. She underwent limbal transplantation. The anterior chamber reformed postoperatively and her intraocular pressure was normal. At 12 months after transplantation, best-corrected visual acuity was 20/500 and the graft-host junction was well apposed.Conclusion:This case shows that corneoscleral melt can occur even 50 years after resection of pterygium combined with postoperative topical MMC.

Pulmonary toxicity after intraperitoneal mitomycin C: a case report of a rare complication of HIPEC

BackgroundCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become a common treatment approach for disseminated appendiceal neoplasms. Systemic absorption of intraperitoneal chemotherapeutics may lead to drug-induced toxicity, most commonly neutropenia. Mitomycin C has been the most commonly used chemotherapeutic in HIPEC for the past several decades.Case presentationHere, we describe a rare pulmonary complication secondary to intraperitoneal administration of mitomycin C.ConclusionsWhile rare, intraperitoneal mitomycin C has the potential to cause serious pulmonary toxicity that should be considered with administration. To our knowledge, this report represents only the second case described in the literature.

Intraperitoneal chemotherapy for gastric cancer with peritoneal disease: experience from Singapore and Japan.

Among advanced gastric cancer cases, peritoneal dissemination is a life-threatening mode of metastasis, and any strategy to control peritoneal metastasis will significantly improve treatment outcomes. Since intraperitoneal administration of anticancer drugs can induce an extremely high concentration of drugs in the peritoneal cavity, intraperitoneal chemotherapy would appear to be a reasonable and promising strategy to control the peritoneal dissemination. However, it has been reported in the past that intraperitoneal administration of mitomycin C or cisplatin resulted in no significant clinical effects against peritoneal metastasis of gastric cancer. In contrast, intraperitoneal paclitaxel is expected to remain inside the peritoneal cavity due to its large molecular weight and fat solubility, leading to a high concentration of the drug in the peritoneal cavity. In fact, promising results in several phase II clinical trials using intraperitoneal paclitaxel have been reported, including a median survival time of 16.2-24.6months and a 1-year overall survival rate of 69-78%. Thereafter, a phase III randomized control study (PHOENIX-GC trial) with intraperitoneal paclitaxel plus systemic S-1 and intravenous paclitaxel in comparison to systemic S-1 plus cisplatin was conducted in Japan. Moreover, a phase II clinical trial of combination chemotherapy of intraperitoneal paclitaxel with systemic capecitabine plus oxaliplatin is currently ongoing in Singapore. In this review, based on clinical experience from Singapore and Japan, the clinical significance of intraperitoneal chemotherapy for gastric cancer with peritoneal disease is discussed.

Developments and current approaches in the treatment of pterygium.

To assess and compare the studies conducted in the literature with recurrence rates and the summary of the justified treatment approaches be presented. Pterygium, a fibrovascular tissue that proceeds from the bulbar conjunctiva towards the cornea, is quite a commonly seen ocular surface deterioration. The treatment is performed through a surgical excision, and the frequent recurrence of this disorder, despite the developments of today, is the major problem experienced in the wake of the surgery. There are various treatment methods applied for the prevention of recurrence; yet, there is no definite view as to what treatment is the most effective one. Since the recurrent pterygium cases are more aggressive than the primary pterygium, it is of great importance to determine the treatment method in which recurrence rate is the lowest. In different studies seen in the literature, there is difficulty in comparing the results due to the fact that the follow-up periods, recurrence criteria and the doses and durations of the medications administered differ from one another. When the literature is reviewed, the bare sclera technique is not used due to the high rate of recurrence, whereas successful results can be achieved through the conjunctival autograft technique. Lower recurrence rates have been reported along with the administration of mitomycin C, 5-FU and other agents that were used as an adjuvant treatment.

A new drug delivery system for Mitomycin C to improve intravesical instillation

The conventional administration of Mitomycin C (MMC) in intravesical instillations has its limitations. In this study, MMC was loaded onto an in situ forming depot consisting of chitosan (CS), β-glycerophosphate (GP) and Fe3O4 magnetic nanoparticles (Fe3O4-MNPs) to improve its effects. The features and effects of this new drug delivery mode were investigated. The new drug delivery system (Fe3O4-MMC-CS/GP) exhibited superior sol-gel transformation and magnetism. Sustained release of MMC was observed both in vitro and in vivo, and the retention, which lasted for 72h in the rat bladder, was further examined using frozen sections. The Cell-Counting Kit-8 (CCK-8) and flow cytometry assays revealed better anti-tumor activity of Fe3O4-MMC-CS/GP compared with the free MMC solution. Animal experiments showed that Fe3O4-MMC-CS/GP provided a favorable survival rate and inhibited the growth of bladder tumors. Moreover, this drug delivery system enhanced tumor cell apoptosis compared with the conventional route of MMC administration in rats.

Sequential bacillus Calmette-Guérin/Electromotive Drug Administration of Mitomycin C as the Standard Intravesical Regimen in High Risk Nonmuscle Invasive Bladder Cancer: 2-Year Outcomes

Sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C is reported to be superior to bacillus Calmette-Guérin alone but it has not been widely adopted. We aimed to determine the efficacy and tolerability of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in high risk, nonmuscle invasive bladder cancer. Starting in 2009 bacillus Calmette-Guérin/electromotive drug administration of mitomycin C was introduced as the standard induction regime in patients with high risk, nonmuscle invasive bladder cancer undergoing bladder conservation. As induction bacillus Calmette-Guérin was administered in weeks 1 and 2. Mitomycin C was administered in electromotive fashion (40 mg and 20 mA current for 30 minutes) in week 3 and repeated thrice for a total of 9 weeks. As maintenance 3 doses of bacillus Calmette-Guérin were given 3 months after induction and then every 6 months for 3 years. Outcome measures were disease recurrence at first check, 1 and 2-year cystoscopy, and treatment tolerability. Of the 151 patients with high risk, nonmuscle invasive bladder cancer treated between June 2009 and 2013, 44 underwent primary cystectomy and 107 received sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C. Disease was high grade Ta/T1 in 86 patients (80%), of whom 34(32%) also had carcinoma in situ. A total of 19 patients (18%) had primary carcinoma in situ and 2 had recurrent large volume, low grade disease. Of 107 patients 104 underwent first check cystoscopy, including 90 (87%) who were clear. Of the 90 complete responders 86 underwent 1-year cystoscopy, including 74 (86%) who were recurrence-free. Of the 74 patients 71 underwent 2-year cystoscopy, of whom 66 (93%) remained recurrence-free. The full induction schedule was not completed in 30 patients (28%), including 16 and 14 with minor and major schedule alterations, respectively. There was no difference in recurrence between patients who received a full vs a reduced induction schedule. This study confirms the excellent oncologic efficacy of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in cases of high risk, nonmuscle invasive bladder cancer. Tolerability is a challenge but alterations to the 9-week schedule appeared to have a negligible impact on outcomes.

A clinical study of comparison of pterygium surgery with and without Mitomycin- C on bare sclera technique

Introduction: A pterygium is a triangular wedge of fibro-vascular conjunctival tissue that appears on the epibulbar conjunctiva, which can be removed by various methods. Recurrence of Pterygium after exicision is a very common problem encountered by ophthalmologist. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after application of intraoperative mitomycin C (0.04%). Method: This is a prospective study of fifty eyes in fifty patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C(25 patients) and without using mitomycin c(25 patients) during September 20014—September 2015 in the ophthalmology department at Jhalawar medical college, Jhalawar( raj.). 0.04% Mitomycin applied to bare sclera after excision for two minutes by swab sticks. Postoperative follow up period was 6 months. Outcomes measured in the form of recurrence and complications were analyzed. Results: In Group A with use of mitomycin C there was no recurrence after 6 months follow-up while in Group B recurrence was seen in 5 patients within 3-6 months, however in group A, 1 patient had scleral thinning. Conclusion: Intraoperative administration of mitomycin C 0.04% is safe and effective to prevent pterygium recurrences.

Beneficial effects of perioperative chemotherapy for pancreatic cancer.

448 Background: We retrospectively assessed the benefits of 5-fluorouracil (5-FU)- and heparin-based portal infusion chemotherapy (PI) combined with systemic administration of mitomycin C (MMC) and cisplatin (CDDP) for 4 weeks following surgery (PI4W). The goal was to determine if this treatment prevented liver metastasis and improved survival for patients with potentially curative resection of pancreatic cancer. Methods: 263 patients who underwent pancreatectomy from January 1985 to December 2013 were treated. Of these cases, 50 patients received portal infusion with 5-FU (250 mg/day) for 2 weeks (PI2W) following surgery (1985 `2001 Group A), while 94 patients received PI4W therapy (250 mg/day of 5-FU with 2,000 IU/day of heparin for 4 weeks, 4 mg MMC on days 6, 13, 20, 27, and 10 mg CDDP on days 7, 14, 21, 28)(2001 `2013 Group B). The remaining 119 patients (Ct) without adjuvant therapy during the perioperative period divided Group A (n=58) and Group B (n=61). Results: The cumulative overall survival rate in the PI2W was significantly higher than those in Ct of Group A. The cumulative overall survival rate in the PI4W also was significantly higher than those in Ct of Group B. Furthermore, in the PI4W group, the rate of liver metastasis is lower than Ct. Conclusions: PI therapy after surgery, especially PI4W, could become a promising adjuvant therapy in patients with potentially curative resection of pancreatic cancer. Clinical trial information: 000002976.

Evidence for clinical efficacy of mitomycin C in heavily pretreated ovarian cancer patients carrying germ-line BRCA1 mutation.

Ovarian carcinomas (OC) arising in BRCA1 and BRCA2 mutation carriers demonstrate pronounced sensitivity to platinum-based therapy due to deficiency of double-strand break DNA repair. However, the choice of subsequent treatment lines for this category of women remains complicated. We considered mitomycin C for heavily pretreated hereditary OC patients, based on multiple evidence for BRCA-specific activity of this drug. Twelve patients carrying BRCA1 germ-line mutation were included in the study. All women had a history of surgical intervention followed by adjuvant platinum-based therapy; three patients also received platinating agents prior the operation. The number of preceding treatment lines for metastatic disease was one for three patients, two for four patients, three for two patients, four for two patients and six for one woman. Administration of mitomycin C (10 mg/m2, every 4 weeks) resulted in one complete response (duration 36 weeks), two partial responses (duration 36 and 48 weeks) and six instances of disease stabilization (duration 12, 16, 20, 24, 24 and 24 weeks). In addition, three patients with the stable disease showed a decline of CA-125 level. We conclude that mitomycin C may deserve further evaluation in clinical trials involving BRCA1/2-related cancers.

Toll-Like Receptor 6 and Connective Tissue Growth Factor Are Significantly Upregulated in Mitomycin-C-Treated Urothelial Carcinoma Cells Under Hydrostatic Pressure Stimulation

Urothelial carcinoma (UC) is the most common histologic subtype of bladder cancer. The administration of mitomycin C (MMC) into the bladder after transurethral resection of the bladder tumor (TURBT) is a common treatment strategy for preventing recurrence after surgery. We previously applied hydrostatic pressure combined with MMC in UC cells and found that hydrostatic pressure synergistically enhanced MMC-induced UC cell apoptosis through the Fas/FasL pathways. To understand the alteration of gene expressions in UC cells caused by hydrostatic pressure and MMC, oligonucleotide microarray was used to explore all the differentially expressed genes. After bioinformatics analysis and gene annotation, Toll-like receptor 6 (TLR6) and connective tissue growth factor (CTGF) showed significant upregulation among altered genes, and their gene and protein expressions with each treatment of UC cells were validated by quantitative real-time PCR and immunoblotting. Under treatment with MMC and hydrostatic pressure, UC cells showed increasing apoptosis using extrinsic pathways through upregulation of TLR6 and CTGF.

Determination of mitomycin C in rabbit plasma by ultra-high performance liquid chromatography-tandem mass spectrometry

An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of mitomycin C (MMC) in rabbit plasma was established. The blank rabbit plasma sample solutions added with mitomycin C and triamcinolone acetonide (internal standard, IS) were prepared. The solutions containing MMC and IS were extracted from the plasma with ethyl acetate using liquid-liquid extraction method. A Hypersil Gold C18 column (50 mm x 2.1 mm, 1.9 microm) was employed and the column temperature was set at 35 degrees C. The isocratic elution of methanol and 0.1% (v/v) formic acid aqueous solution as mobile phase was performed at a flow rate of 0.2 mL/min, and a rapid separation was completed within 3 min. The electrospray was operated in the positive ionization mode and the MMC and IS were identified in selected reaction monitoring (SRM) mode. The monitoring ions of MMC and IS were m/z 335. 2 --> 242.2 and m/z 435.2 --> 397. 3/415.2, respectively, which were used to qualify and quantify the targets by the method of matrix-matched standard solution. The calibration curve showed good linearity within the mass concentrations of 1 to 1 000 microg/L (r = 0.997 8, weighting: 1/x2). The limit of detection (S/N = 3) was 0.2 microg/L. The recoveries were from 85% to 115% at the spiked levels of 1, 5, 100 and 800 microg/L, and the relative standard deviations (RSDs) of intra- and inter-day were both less than 15%. The method can meet the determination requirements of biological samples, and can be used for the determination of mitomycin C in rabbit plasma after the administration of mitomycin C. The method is selective, sensitive, convenient, rapid and reproducible in the determination of mitomycin C, and also can be used for the pharmacokinetics research of mitomycin C in plasma.

Effect of intratympanic mitomycin C on the development of cholesteatoma and otitis media in rats

To determine whether the administration of mitomycin C prevents propylene glycol exposure from inducing middle-ear cholesteatoma and otitis media, in a rat model. Twenty-four Wistar rats underwent intratympanic injections on days 1, 8 and 15, via the tympanic membrane pars tensa, in both the right and left ears. The right ear injection solution contained 50 per cent propylene glycol, gentamicin and saline (0.9 per cent), while the left ear solution contained 50 per cent propylene glycol, gentamicin and mitomycin C. Animals were sacrificed and examined. There were statistically significant differences between the control and experimental groups for tympanic bulla mucosal thickness (p = 0.004) but not for tympanic membrane thickness (p = 0.371), otomicroscopic findings (p = 0.262), or the presence of exudate (p = 0.125), fibrosis (p = 1.000) or cholesteatoma (p = 0.687). Intratympanic mitomycin C was ineffective in preventing middle-ear cholesteatoma and otitis media in this rat model.

Prevention of Epidural Fibrosis in Rats by Local Administration of Mitomycin C or Daunorubicin.

Epineural adhesion after peripheral nerve surgery is common. The purpose of this study was to evaluate the macroscopic and histopathologic effects of topical mitomycin C and daunorubicin on epineural scar formation. In this study, we used 15 rats (30 nerves). Two test groups and one control group were created. Sciatic nerve exposure was created bilaterally in each group (30 nerve examinations in total). In experimental group 1, cotton pads that had absorbed mitomycin C (0.5 mg/ml) were placed onto the nerves for 5 minutes while in experimental group 2, cotton pads that had absorbed daunorubicin (0.2 mg/ml) were placed onto the nerves for 5 minutes and cotton pads that had absorbed saline were applied to the control group. Eight weeks after the first surgery, surgical dissection was performed for the evaluation of neurolysis sites. Epineural adhesions were classified utilizing a numerical grading layout. We did not find any adverse effect with topically applied mitomycin C and daunorubicin. Within the 3 groups, no significant difference was seen in skin and fascia-muscle cavity closure (p > 0.05). Macroscopically, mitomycin C and daunorubicin decreased the adhesion of sciatic nerve to adjacent structures. There was intensive epineural scar formation in the control group. Scar tissue thickness and fibroblast/fibrocyte cell number were less in the two test groups compared with the control group (p < 0.001). There was no statistical difference between the two test groups. Epineural scar formation after peripheral nerve surgery may be reduced by using topical application of mitomycin C and daunorubicin.

The Protective Effect of Berberis aristata against Mitochondrial Dysfunction Induced due to Co-administration of Mitomycin C and Cisplatin

Background: The combination of mitomycin C and cisplatin was proved to be beneficial in the treatment of lung cancer, breast cancer, anal carcinoma and human cervical cancer treatment. However, dose related toxicity happens to be one of the major concerns the treatment, leading to its discontinuation, although the patient’s response is encouraging. The aim of the present investigation was to study the protective effects of Berberis aristata (10 mg/kg body weight) on the mitochondrial dysfunction caused due to administration of mitomycin C (2 mg/kg body wt, i.p) and cisplatin (12 mg/kg body wt, i.p). Methods: We have investigated the effects and protective effects on oxidative phosphorylation enzymes, of the electron transport system, lipid peroxidation and phospholipid composition in liver and kidney mitochondria. Results: Co-administration of mitomycin C and cisplatin resulted in significant decrease in active respiration (State 3 Respiration), Respiratory Control Ratio (RCR) and P/O ratio’s using either succinate or glutamate plus malate as substrate. Altered enzyme activities of NADH dehydrogenase, succinate dehydrogenase, succinatecytochrome c reductase, NADH-cytochrome c reductase, cytochrome c oxidase was observed. The level of lipid peroxides was increased, and with a significant decrease in phospholipid content. Prior administration of Berberis aristata protected against observed mitochondrial dysfunction. Conclusions: We believe that prior administration of Berberis aristata could reduce the damage to mitochondrial function, by scavenging free radicals and thereby, preventing uncoupling of oxidative phosphorylation, deactivation of enzymes of electron transport chain, generation of lipid peroxides, oxidation of phospholipids ultimately inhibiting the signaling wave propagation to the mitochondria death receptor (membrane bound cytochrome c), which generally leads to apoptosis.